tbuckley/cabot-search huggingface dataset:
TRIM35-mediated degradation of nuclear PKM2 destabilizes GATA4/6 and induces P53 in cardiomyocytes to promote heart failure
Authors: Maria Areli Lorenzana-Carrillo, Keshav Gopal, Nikole J. Byrne, Saymon Tejay, Bruno Saleme, Subhash K. Das, Yongneng Zhang, Alois Haromy, Farah Eaton, Michelle Mendiola Pla, Dawn E. Bowles, Jason R. B. Dyck, John R. Ussher, Evangelos D. Michelakis, Gopinath Sutendra
Journal: Science Translational Medicine (2022)

Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that translocates to the nucleus to regulate transcription factors in different tissues or pathologic states. Although studied extensively in cancer, its biological role in the heart remains unresolved. PKM1 is more abundant than the PKM2 isoform in cardiomyocytes, and thus, we speculated that PKM2 is not genetically redundant to PKM1 and may be critical in regulating cardiomyocyte-specific transcription factors important for cardiac survival. Here, we showed that nuclear PKM2 ( S37 P-PKM2) in cardiomyocytes interacts with prosurvival and proapoptotic transcription factors, including GATA4, GATA6, and P53. Cardiomyocyte-specific PKM2-deficient mice ( Pkm2 Mut Cre + ) developed age-dependent dilated cardiac dysfunction and had decreased amounts of GATA4 and GATA6 (GATA4/6) but increased amounts of P53 compared to Control Cre + hearts. Nuclear PKM2 prevented caspase-1–dependent cleavage and degradation of GATA4/6 while also providing a molecular platform for MDM2-mediated reduction of P53. In a preclinical heart failure mouse model, nuclear PKM2 and GATA4/6 were decreased, whereas P53 was increased in cardiomyocytes. Loss of nuclear PKM2 was ubiquitination dependent and associated with the induction of the E3 ubiquitin ligase TRIM35. In mice, cardiomyocyte-specific TRIM35 overexpression resulted in decreased S37 P-PKM2 and GATA4/6 along with increased P53 in cardiomyocytes compared to littermate controls and similar cardiac dysfunction to Pkm2 Mut Cre + mice. In patients with dilated left ventricles, increase in TRIM35 was associated with decreased S37 P-PKM2 and GATA4/6 and increased P53. This study supports a previously unrecognized role for PKM2 as a molecular platform that mediates cell signaling events essential for cardiac survival.
2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines
Authors: Eric M. Isselbacher, Ourania Preventza, James Hamilton Black, John G. Augoustides, Adam W. Beck, Michael A. Bolen, Alan C. Braverman, Bruce E. Bray, Maya M. Brown-Zimmerman, Edward P. Chen, Tyrone J. Collins, Abe DeAnda, Christina L. Fanola, Leonard N. Girardi, Caitlin W. Hicks, Dawn S. Hui, William Schuyler Jones, Vidyasagar Kalahasti, Karen M. Kim, Dianna M. Milewicz, Gustavo S. Oderich, Laura Ogbechie, Susan B. Promes, Elsie Gyang Ross, Marc L. Schermerhorn, Sabrina Singleton Times, Elaine E. Tseng, Grace J. Wang, Y. Joseph Woo, David P. Faxon, Gilbert R. Upchurch, Aaron W. Aday, Ali Azizzadeh, Michael Boisen, Beau Hawkins, Christopher M. Kramer, Jessica G.Y. Luc, Thomas E. MacGillivray, S. Christopher Malaisrie, Kathryn Osteen, Himanshu J. Patel, Parag J. Patel, Wanda M. Popescu, Evelio Rodriguez, Rebecca Sorber, Philip S. Tsao, Annabelle Santos Volgman
Journal: Circulation (2022)

The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes).
Ultrasound diagnosis of dirofilariasis: case reports
Authors: M. A. Asriyants, O. V. Astafieva, A. V. Pomortsev, E. K. Gordeeva
Journal: Radiology - Practice (2022)

Dirofilariasis is a transmissible zoonotic biohelminthiasis caused by nematodes that parasitize the lymphatic system and subcutaneous tissue. This paper presents cases of dirofilariasis lesions of the soft tissues of the face and eyes. Purpose: to demonstrate the possibility of ultrasonic diagnosis of dirofilariasis of soft tissues of the face. Materials and methods. Dirofilaria can affect the soft tissues of the face, eyes, mammary glands, buttocks. Patients complained of swelling, induration and hyperemia in the soft tissues of the face. Ultrasound was performed, which determined echoes characteristic of helminthic parasites, parasites were removed, the belonging of the macropreparation to dirofilaria type Dirofilaria repens was confirmed by the laboratory of the SES of Krasnodar. Results: the possibilities of ultrasound examination of the eyes and soft tissues were demonstrated, and the characteristic echo signs in dirofilariasis were identified.
The Benign Sphenoid Sinus Fungal Ball in a Mask of Sphenoid Non-specific Sinusitis by Means of Computer Tomography Imaging (Clinical Case)
Authors: T. Yu. Malysheva, V. V. Viktorov, S. V. Fedorov, D. A. Shcherbakov, N. V. Klimova
Journal: Radiology - Practice (2022)

A clinical case of sphenoid sinus fungal ball was presented and interested for non-typical computer tomography imaging features, resulting in the patient was threatening from nonspecific sphenoid sinusitis throughout the year. A long persisted fungal ball became malignant. The imaging data of sphenoid sinus fungal ball in the onset and manifestation of the disease was analyzed. By presentation of the clinical case the importance of analyzing sinus bone wall remodeling by means of computer tomography and using of magnetic resonance imaging in a case of a timely fashion diagnosis of sphenoid fungal ball was shown.
Exploring the role of intratendinous pressure in the pathogenesis of tendon pathology: a narrative review and conceptual framework
Authors: Lauren Pringels, Jill L Cook, Erik Witvrouw, Arne Burssens, Luc Vanden Bossche, Evi Wezenbeek
Journal: British Journal of Sports Medicine (2022)

Despite the high prevalence of tendon pathology in athletes, the underlying pathogenesis is still poorly understood. Various aetiological theories have been presented and rejected in the past, but the tendon cell response model still holds true. This model describes how the tendon cell is the key regulator of the extracellular matrix and how pathology is induced by a failed adaptation to a disturbance of tissue homeostasis. Such failure has been attributed to various kinds of stressors (eg, mechanical, thermal and ischaemic), but crucial elements seem to be missing to fully understand the pathogenesis. Importantly, a disturbance of tissue pressure homeostasis has not yet been considered a possible factor, despite it being associated with numerous pathologies. Therefore, we conducted an extensive narrative literature review on the possible role of intratendinous pressure in the pathogenesis of tendon pathology. This review explores the current understanding of pressure dynamics and the role of tissue pressure in the pathogenesis of other disorders with structural similarities to tendons. By bridging these insights with known structural changes that occur in tendon pathology, a conceptual model was constituted. This model provides an overview of the possible mechanism of how an increase in intratendinous pressure might be involved in the development and progression of tendon pathology and contribute to tendon pain. In addition, some therapies that could reduce intratendinous pressure and accelerate tendon healing are proposed. Further experimental research is encouraged to investigate our hypotheses and to initiate debate on the relevance of intratendinous pressure in tendon pathology.
Close collaboration between pathologists and intensivists to understand (not just) coronavirus disease
Authors: Christoph Brochhausen, Thomas Bein, Vittorio Fineschi
Journal: Intensive Care Medicine (2022)

Struggling with an unknown entity-challenge for intensivistsDespite improvements in imaging and diagnostic procedures in critically ill patients presenting with organ failure, uncertainty often exists with regard to the exact diagnosis and a corresponding targeted therapy.Recent studies have demonstrated an error rate of up to 44% in diagnosis after autopsy [1].The novel coronavirus disease 2019 (COVID-19)-especially the associated severe acute respiratory syndrome-led to a rush of critically ill patients to intensive care units, which were neither prepared in terms of staff and logistic demands nor in terms of specific knowledge of such a new disease.After a period of uncertainty and overload, more clinical insights into the 'nature' of the COVID-19 were revealed by autopsies.Assisted by pathologists, intensivists learnt to transfer such knowledge into therapeutic improvement.Specifically, the frequency of deep venous thrombosis or pulmonary embolism led to the adoption of an anticoagulation strategy.Autopsies, histopathological analyses, molecular findings, results of immunohistochemistry, and ultrastructural analyses had a direct impact, and, consequently, the pandemic started a new effective interdisciplinary collaboration, which should continue even beyond the pandemic.
The Impact of Intensified CNS-Directed Therapy on Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation
Authors: Lisa M. Jacola, Heather M. Conklin, Kevin R. Krull, Deqing Pei, Cheng Cheng, Wilburn E. Reddick, Ching-Hon Pui, Sima Jeha
Journal: Journal of Clinical Oncology (2022)

Findings from St Jude Total Therapy Study 16 (Total 16) showed early intensification of triple intrathecal therapy (ITT) improved CNS disease control for children with newly diagnosed acute lymphoblastic leukemia (ALL) at the greatest risk of CNS relapse. We examined the impact of this treatment on end-of-therapy neurocognitive outcomes.Between 2007 and 2017, 400 (83.5%) of 479 eligible patients treated with Total 16 risk-directed chemotherapy completed protocol-directed neurocognitive testing at the end of therapy. Intensified ITT was defined as ≥ 21 cumulative doses for patients with low-risk ALL (n = 70/194) and ≥ 27 doses for those with standard-to-high risk ALL (n = 81/206).Compared with age-normative expectations, the overall group had significantly lower estimated intelligence quotient (P < .0001), attention (P = .0051), working memory (P = .0001), processing speed (P = .0002), fine motor speed (P = .0001), and math (P = .0087). Caregiver ratings of patient functioning showed elevated risk for problems in attention (P = .0173), executive function (P = .0001), and adaptive skills (P = .0001). Among the low-risk treatment group, there were no significant differences between patients treated with or without intensified ITT (all P's >.10). Among patients with standard-to-high risk ALL, those treated with intensified ITT had poorer working memory (P = .0328) and fine motor speed (P = .0403), and elevated ratings of inattention (P = .0189) and executive dysfunction (P = .0245). In the standard-to-high risk group, females treated with intensified ITT had lower working memory scores. Public insurance status was associated with worse neurocognitive outcomes in both treatment groups.Standard-to-high risk patients treated with intensified ITT are at moderately increased risk for neurocognitive problems. The findings suggest a threshold effect for ITT exposure, which can inform the design of future clinical trials and approaches to neurocognitive monitoring and intervention.
Incidence and clinical factors associated with ulceration in infantile hemangiomas
Authors: Esteban Fernández Faith, Sonal D Shah, Mitchell Braun, Elena Pope, Irene Lara-Corrales, Patricia M Witman, Katya Harfmann, Flora Bradley, Rohali Keesari, Kenneth Jackson, Alexandra Hallagan, Ilona J Frieden
Journal: Journal of the American Academy of Dermatology (2022)
Virtual reality in the diagnostic and therapy for mental disorders: A systematic review
Authors: Annika Wiebe, Kyra Kannen, Benjamin Selaskowski, Aylin Mehren, Ann-Kathrin Thöne, Lisa Pramme, Nike Blumenthal, Mengtong Li, Laura Asché, Stephan Jonas, Katharina Bey, Marcel Schulze, Maria Steffens, Max Christian Pensel, Matthias Guth, Felicia Rohlfsen, Mogda Ekhlas, Helena Lügering, Helena Fileccia, Julian Pakos, Silke Lux, Alexandra Philipsen, Niclas Braun
Journal: Clinical Psychology Review (2022)
Association of kidney function and brain health: A systematic review and meta-analysis of cohort studies
Authors: Xingyao Tang, Yi-Peng Han, Yin-He Chai, Hong-Jian Gong, Hui Xu, Ikramulhaq Patel, Yu-Shun Qiao, Jin-Yan Zhang, Marly Augusto Cardoso, Jian-Bo Zhou
Journal: Ageing Research Reviews (2022)

This study aimed to evaluate the bidirectional association between the kidney dysfunction and the brain health, including structural and functional abnormalities.Systematic review and meta-analysis with network meta-analysis for outcomes with different estimated glomerular filtration rate (eGFR) ranges.PubMed, Embase database, Cochrane library and Web of Science (up to Dec. 2021).Longitudinal studies that provided evidence of the impact of kidney function estimated from eGFR and urine albumin-to-creatinine ratio (UACR) or chronic kidney disease (CKD) on structural and functional brain abnormalities, and those that provided evidence of the opposite relationship. Studies with study population mean age under 18 years old were excluded.Two independent reviewers screened the included studies, extracted the data, and assessed the risk of bias. We performed a random-effects meta-analysis and a network meta-analysis for outcomes with compatible data. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale criteria (NOS). Subgroup and sensitivity analyses were conducted to explore heterogeneity in the meta-analyses. Inconsistency analyses using the node-splitting method were performed to confirm the results of network meta-analysis.A total of 53 studies with 3037,357 participants were included in the current systematic review. Among these, 16 provided evidence of structural brain abnormalities, and 38 provided evidence of cognitive impairment and dementia. Analysis of evidence of categorical kidney function showed a positive association between kidney dysfunction and cerebral small vessel disease (cSVD) (relative risk (RR) 1.77, 95% confidence interval (CI) 1.40-2.24, I2 = 0.0%), but such results were not found in the analyses of evidence where the kidney function was measured as a continuous variable. Meanwhile, analysis of 28 prior longitudinal studies with 194 compatible sets of data showed that the worse kidney function as categorical variables was related to a greater risk of global brain cognitive disorder (RR 1.28, 95% CI 1.20-1.36, I2 = 82.5%).In this systematic review and meta-analysis, we found a positive association between CKD and functional brain disorders. However, the relationship between the kidney dysfunction and structural abnormalities in the brain remains controversial. As for the opposite relationship, structural brain abnormalities, especially cerebral microbleeds and silent infarction, but not functional brain abnormalities, are associated with worse renal function. In addition, a higher UACR, but not a lower eGFR, was associated with a higher risk of Alzheimer's disease and vascular dementia.
A novel Nanocellulose-Gelatin-AS-IV external stent resists EndMT by activating autophagy to prevent restenosis of grafts
Authors: Tianshu Chu, Qingye Li, Chun Dai, Xiang Li, Xiang Kong, Yangming Fan, Hongyan Yin, Jianjun Ge
Journal: Bioactive Materials (2022)

Vein grafts are widely used for coronary artery bypass grafting and hemodialysis access, but restenosis remains the "Achilles' heel" of these treatments. An extravascular stent is one wrapped around the vein graft and provides mechanical strength; it can buffer high arterial pressure and secondary vascular dilation of the vein to prevent restenosis. In this study, we developed a novel Nanocellulose-gelatin hydrogel, loaded with the drug Astragaloside IV (AS-IV) as an extravascular scaffold to investigate its ability to reduce restenosis. We found that the excellent physical and chemical properties of the drug AS-IV loaded Nanocellulose-gelatin hydrogel external stent limit graft vein expansion and make the stent biocompatible. We also found it can prevent restenosis by resisting endothelial-to-mesenchymal transition (EndMT) in vitro. It does so by activating autophagy, and AS-IV can enhance this effect both in vivo and in vitro. This study has added to existing research on the mechanism of extravascular stents in preventing restenosis of grafted veins. Furthermore, we have developed a novel extravascular stent for the prevention and treatment of restenosis. This will help optimize the clinical treatment plan of external stents and improve the prognosis in patients with vein grafts.
A novel biological sources consistency evaluation method reveals high level of biodiversity within wild natural medicine: A case study of Amynthas earthworms as “Guang Dilong”
Authors: Zhimei Xing, Han Gao, Dan Wang, Ye Shang, Tenukeguli Tuliebieke, Jibao Jiang, Chunxiao Li, Hong Wang, Zhenguo Li, Lifu Jia, Yongsheng Wu, Dandan Wang, Wenzhi Yang, Yanxu Chang, Xiaoying Zhang, Liuwei Xu, Chao Jiang, Luqi Huang, Xiaoxuan Tian
Journal: Acta Pharmaceutica Sinica B (2022)

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.
Massive furunculoid myiasis in a traveller after a trip to Uganda
Authors: Pablo Villagrasa-Boli, Sara Martínez-Cisneros, Elena Aura Bularca, Beatriz Lopez-Alonso, Sergio García González, Mariano Ara-Martín, José Luis Juan-Bañón, Antonio Beltrán-Rosel
Journal: Clinical Microbiology and Infection (2022)
Engineered tumor cell-derived vaccines against cancer: The art of combating poison with poison
Authors: Xinyi Zhang, Hengqing Cui, Wenjun Zhang, Zhaoshen Li, Jie Gao
Journal: Bioactive Materials (2022)

Tumor vaccination is a promising approach for tumor immunotherapy because it presents high specificity and few side effects. However, tumor vaccines that contain only a single tumor antigen can allow immune system evasion by tumor variants. Tumor antigens are complex and heterogeneous, and identifying a single antigen that is uniformly expressed by tumor cells is challenging. Whole tumor cells can produce comprehensive antigens that trigger extensive tumor-specific immune responses. Therefore, tumor cells are an ideal source of antigens for tumor vaccines. A better understanding of tumor cell-derived vaccines and their characteristics, along with the development of new technologies for antigen delivery, can help improve vaccine design. In this review, we summarize the recent advances in tumor cell-derived vaccines in cancer immunotherapy and highlight the different types of engineered approaches, mechanisms, administration methods, and future perspectives. We discuss tumor cell-derived vaccines, including whole tumor cell components, extracellular vesicles, and cell membrane-encapsulated nanoparticles. Tumor cell-derived vaccines contain multiple tumor antigens and can induce extensive and potent tumor immune responses. However, they should be engineered to overcome limitations such as insufficient immunogenicity and weak targeting. The genetic and chemical engineering of tumor cell-derived vaccines can greatly enhance their targeting, intelligence, and functionality, thereby realizing stronger tumor immunotherapy effects. Further advances in materials science, biomedicine, and oncology can facilitate the clinical translation of tumor cell-derived vaccines.
Comparison of two chemotherapy regimens in patients with newly diagnosed Ewing sarcoma (EE2012): an open-label, randomised, phase 3 trial
Authors: Bernadette Brennan, Laura Kirton, Perrine Marec-Bérard, Nathalie Gaspar, Valerie Laurence, Javier Martín-Broto, Ana Sastre, Hans Gelderblom, Cormac Owens, Nicola Fenwick, Sandra Strauss, Veronica Moroz, Jeremy Whelan, Keith Wheatley
Journal: The Lancet (2022)
Dynamic crosslinked polymeric nano-prodrugs for highly selective synergistic chemotherapy
Authors: Shi Wang, Yining Song, Jingge Ma, Xinyang Chen, Yuanhui Guan, Hui Peng, Guoqing Yan, Rupei Tang
Journal: Asian Journal of Pharmaceutical Sciences (2022)

To achieve highly selective synergistic chemotherapy attractive for clinical translation, the precise polymeric nano-prodrugs (PPD-NPs) were successfully constructed via the facile crosslinking reaction between pH-sensitive poly(ortho ester)s and reduction-sensitive small molecule synergistic prodrug (Pt(IV)-1). PPD-NPs endowed the defined structure and high drug loading of cisplatin and demethylcantharidin (DMC). Moreover, PPD-NPs exhibited steady long-term storage and circulation via the crosslinked structure, suitable negative potentials and low critical micelle concentration (CMC), improved selective tumour accumulation and cellular internalization via dynamic size transition and surficial amino protonation at tumoural extracellular pH, promoted efficient disintegration and drug release at tumoural intracellular pH/glutathione, and enhanced cytotoxicity via the synergistic effect between cisplatin and DMC with the feed ratio of 1:2, achieving significant tumour suppression while decreasing the side effects. Thus, the dynamic crosslinked polymeric nano-prodrugs exhibit tremendous potential for clinically targeted synergistic cancer therapy.